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Highlights & Assessment: Gordon McVie on ECCO15-ESMO34

A flying start to the new joint ECCO-ESMO conference: great weather, an inspiring simultaneous Berlin marathon, and 15,000 people exchanging ideas in the lecture halls, poster sessions, and corridors alike.

The big splash was the impressive presidential kickoff hosted by oncologist and surgeon Professor Peter Schlag from the Charité University Medicine, Berlin, detailing his expansive cancer hospital and the important work it conducts.

Alexander Eggermont, president of the European CanCer Organisation, followed by highlighting the specially selected “oncopolicy” sessions, along with the “young oncologist” and “patient advocacy” tracks.

He also launched the European Academy of Cancer Sciences, a new initiative designed to inform and educate policymakers at national, European, and global levels about the needs of the oncology community, to keep the interests of cancer patients at the forefront of the policy agenda, and avoid policy decisions that have a negative impact on the practice of oncology medicine.

José Baselga, president of the European Society for Medical Oncology, pledged that this was not just a one-off meeting between ESMO and ECCO, but rather the start of an important organizational shift, seeing people come together from all the disciplines involved in cancer care - including most importantly, the patients—in a serious way, to make a difference and make an impact on cancer survival rates in Europe (more details on p. 27).

As the first day played out, the science began to trickle in, with results on pemetrexed in lung cancer. Giving pemetrexed maintenance therapy to patients with non-small-cell lung cancer who have not had disease progression after initial platinum-based chemotherapy was found to improve both overall and progression-free survival.

Other standout presentations focused on dose-dense chemotherapy in ovarian cancer, a new drug for primary central nervous system lymphoma, and ipilimumab in melanoma. All this as well as new data on upfront aromatase inhibitors in adjuvant hormone-sensitive breast cancer, where it seems letrozole is setting the pace.

There was also a lot of interest in bone-sparing—possibly even bone-building—drugs like the old favorite zoledronic acid. This now seems to be not just a bone-sparing drug, but also one with anti-cancer properties.

New data also showed that denosumab was superior to zoledronic acid in delaying time to the first on-study skeletal-related events in advanced cancer patients with bone metastases, and also reduced fracture risk in men with non-metastatic prostate cancer undergoing androgen-deprivation therapy.

Chemoprevention in Bowel Cancer

I have to say that the star of the first couple of days was Professor John Burn, from the Newcastle Institute of Human Genetics, who—with the patience of a saint—completed a long, drawn-out chemoprevention survey in patients with a very high familial risk of bowel cancer. This disease is quite common and generally presents too late for cure, so catching patients early—particularly those with a genetic predisposition—is absolutely vital.

There has been a lot of evidence around for some time that aspirin might act to prevent bowel cancer in patients with risk factors for the disease. Thus, 14 years ago Professor Burn set out on a large study of patients with Lynch syndrome—who were therefore at special risk—and randomized them to aspirin versus placebo.

His team studied adenomas on the colon walls of some 1,000 participants and found no effect at 10 years. The article went to the New England Journal of Medicine and Burn lost funding, but he continued to concentrate on the more important end point: cancer.

At Berlin he showed, for the first time, that if you look at the patients who get cancer of the colon, rather than just adenomas, the preventative effect of aspirin becomes apparent: 17 volunteers in the aspirin group went on to get bowel cancer and 52 in the placebo group. There was also a reduction in endometrial cancer.

This has immense implications for chemoprevention studies looking at other genetically linked conditions, for example in ovarian and maybe even breast, so this whole area is taking off.

Big Guns & New Approaches

As the conference progressed, the big guns turned up to tell us how you go about inventing new approaches in cancer and then take them through to the clinic.

In a plenary lecture, Sir David Lane—one of the co-inventors of p53—gave a history of his work right up to the present day, where p53 is now being used in the clinic in a variety of extraordinary ways.

Then we had the oncogene cloner, Dr. Mariano Barbacid, who heads the innovative Spanish National Cancer Institute in Madrid, emphasizing that we should avoid rushing headlong in to the clinic. We know there are many drugs in the pipeline and also that we can never get them all tested as single agents within three or four years, and certainly not in combination.

Barbacid is therefore pleading for the use of more human look-alike models. He's got a whole host of genetically modified animals that he believes will be far more helpful to the planning of early clinical trials of both single agents and combinations.

American Lifetime Achievement Award

There was also a historic moment when the European CanCer Organisation gave a lifetime achievement award to an American. The distinguished Dr. Marge Foti has been the chief executive of the American Association of Cancer Research for many years, with great success. Dr. Foti has expanded the organization by thousands of members, around half of whom are clinicians or translational scientists, as well as establishing several new publications to aid cancer communication.

Where Money Should Go

What should we be spending our research dollars, pounds, and Euros on? That was the subject of a provocative talk by Professor Richard Sullivan of King's College, London, who questioned the mechanisms for the prioritization of research. He was critical of the imbalance of research funding in favor of the “sexier” subjects such as drug development and drug discovery, to the detriment of prevention research.

Everybody glibly trots out the phrase “prevention is better than cure,” but that's not reflected in the funding from either governments or charities, and Professor Sullivan called for a major change in attitude here.

He discussed prioritizing research carried out across state boundaries. He pointed out that, as we increasingly subdivide disease areas—for example, breast cancer into BRCA1, BRCA2, triple-negative, and Herceptin-positive—so we are inevitably creating smaller, rarer categories of cancers.

Therefore, where it used to be possible to carry out large trials because breast cancer per se was very common, now all these particular subtypes of breast cancers mean that it is difficult to collect enough numbers for the trial—in any one country. And so he stressed the need for cross-boundary pan-European clinical trials, researching into early diagnostics, protection, screening, and prevention.

To tackle this, Professor Sullivan called for an end to the tendency of charities or governments to spend their money on their own country alone. He suggested that patients and donors would understand, if properly informed, that you can solve the question of how to treat a rare cancer only by communicating and collaborating across borders and thus turning an obscure issue into a global one.

Professor Sullivan aimed his final criticism at the establishment, attacking the trend of crowding out young people from the research grants process. Young people with creative new ideas, by definition, are innovative, he said. But sadly, a number of grant agencies are taking the easy way out and giving the money only to the established researchers—the ones with a track record—forgetting perhaps that they too were young investigators at one point. To solve this, he argued, we should go back to looking at the more creative, slightly riskier projects, and to try thinking a little bit more “outside the box.”

Melanoma Excitement

The last days of the conference saw some highlights from the presidential level: Alexander Eggermont drew attention to interesting developments in the molecular genetic pathways within melanoma. A melanoma specialist himself, he said this was “the most exciting time in 30 years” of his own melanoma research because suddenly there are meaningful drug targets.

Professor Eggermont cited the anti-CTL4-antibody ipilimumab which has shown clear evidence of anti-melanoma activity, better than has previously been achieved with either vaccines or cytokines. He is now looking forward to studying combinations—e.g., vaccines plus ipilimumab—and thus advancing the treatments for melanoma even further.

He said he was also excited to hear the follow-up results to the Phase I study reported at ASCO on PLX4032 for the BRAF mutation V600E. Dr. Paul Chapman, from Memorial Sloan-Kettering Cancer Center presented data showing a rapid and dramatic shrinking of metastatic tumors treated with the new compound, which blocks the activity of the cancer-causing mutation of the BRAF gene, implicated in about 50% of melanomas and 5% of colorectal cancers.

In new results from 31 melanoma patients with the BRAF mutation who were treated with 960 mg of PLX4032 twice a day, 64% of those who could be evaluated so far showed partial responses that involved the diameter of tumors shrinking by at least 30% for at least a month, a success story unheard of in melanoma.

A further six of the 22 patients also showed a response, but at the time of the congress presentation, it was too early to say whether the tumors would shrink far enough to meet the criteria for partial response.

Dr. Chapman and his colleagues are now planning both a Phase II and a large Phase III trial involving several hundred patients, to start at the beginning of next year in North America, Europe, and Australia.

The only downside to the PLX4032 story was the news that one or two patients have developed squamous carcinoma of the skin under treatment, so there's a long way to go yet, but the first step is extremely positive.

Next ECCO President

Next up for the ECCO presidency is radiation oncologist Professor Michael Baumann, from the University of Technology, Dresden. His group, including Dr. Dirk de Ruysscher of the University Hospital Maastricht presented the advances made in collecting together tissues such as fibroblasts, plasma, and lymphocytes. Tissues were collected from both sides of the Atlantic, in an EU-funded project named GENEPI (GENEtic pathways for the Prediction of the effects of Irradiation).

The biological material has been gathered from patients who are super-sensitive to radiotherapy, and this is the first time that a collection of such material has been put together and subjected to radiation in the lab.

Hopefully the collection will give reliable biological models, which can then be used to establish what the genetic pathways are in individual people, avoiding unwanted responses to radiotherapy.

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